Method for preparing bis-(substituted tetrahydro-1, 3-oxazino)-methanes



Patented July 28, 1953 UNITED STATES PATENT OFFICE METHOD FOR PREPARING BIS- (SUBSTI- TUTED TETR-AHYDRO 1,3 OXAZINO) METHANES Howard D. Hartough, Pitman, Joseph J. Dickert, Jr., Westville, and Seymour L. Meisel, West Deptford Township, Gloucester County, N. J., assignors to Socony-Vacuum Oil Company, Incorporated, a corporation of New York No Drawing. Application June 22, 1950, Serial No. 169,792

3 Claims.

having a composition o=o RI RIII is reacted with formaldehyde, either as a 35 to 38 per cent aqueous solution of formaldehyde or as a reversible polymer thereof together with a depolymerizer, and a hydrohalide of ammonia or a primary amine or a primary diamine a series of compounds are formed dependent upon molal proportion of the formaldehyde to the olefinic compound. That is to say, when the olefinic compound is reacted with ammonium halide, NH3HX, and formaldehyde in the molal proportion of 2:2:4 the formaldimine and the substituted tetrahydro-1,3oxazine are formed in accordance with Equation 1.

When the molal proportions of olefinic compound, ammonium halide and formaldehyde are 2:225 or amine 1111, the basic amine resulting from the removal of (HX) from derivative II, is reacted in acid solution with another 0.5 mole of formaldehyde the N-methylol derivative III of II is obtained in accordance with the Equation 2.

The reactions illustrated by Equations 1 and 2 require that 5 moles of formaldehyde react with 2 moles of olefinic compound and 2 moles of ammonium halide in order to produce the compound V, i. e., a mole ratio of 2.5:121. However, an amount of formaldehyde in excess of the required formaldehyde olefin ammonium halide ratio of 2.5:1:1 is preferred, since anexcess of formaldehyde leads to increased yields of compound V.

When compound III reacts with'formaldehyde compound IV is formed by the reductive action of the formaldehyde in a manner which can be represented by Equation 3.

+ HCOOH R CH:

Compound III can also react with another mole of compound II forming compound V by the elimination of water in a manner which can be represented by Equation 4.

It has now been discovered that the yield of V, i. e., bis-(tetrahydro-1,3-oxazino)-methanes as the free amines can be markedly improved by employing low operating temperatures; e. g., below 100 C. and preferably below 70 C., and above 55 C., a short reaction time of the order of about 25-30 minutes and an amount of formaldehyde in excess of the molal proportion of 1 to 1 mole of olefinic compound, RRC=RR", say 4 moles of formaldehyde to 1 mole of olefinic compound.

Example I (C21H26N202, mol. wt. calculated 338). Since the theoretical yield of compound V from 0.5 mole of styrene is 0.25 mole it is manifest that the aforementioned yield of 0.13 mole is about 52.0 per cent of theory. The product analyzed: Car bon 74.11 hydrogen 7.75%; nitrogen 8.31%; compared with the calculated values for C21H26N2O2 of carbon-74.55%; hydrogen- 7.69%; nitrogen-8.28%; and a molecular we g t (boiling point method) of 376.

Example II About five moles of styrene, about 20 moles of formaldehyde (as a 36 per cent aqueous solution) and about 10 moles of ammonium chloride were mixed and stirred vigorously. The reaction mixture so obtained was then warmed to 60 C. in about 30 minutes and held at a reaction temperature between 60 and 63 C. for about 27 minutes by means of external cooling. After about 20 minutes the reaction temperature began to drop and the reaction mixture was allowed to cool to room temperature. The reaction mixture stratified into an organic layer and an aqueous layer. The organic layer, amounting to about 13.9 weight per cent of the charge, was separated from the aqueous layer. This organic layer contains unreacted styrene and substituted-1,3-dioxane. The aqueous layer was extracted with ethyl ether and about 0.52 weight per cent of the charge recovered. This material was formaldehyde with small amounts of substituted 1,3-dioxane.

The extracted aqueous layer was then causticized with about 10 moles of sodium hydroxide (as 40 per cent aqueous solution).

About 10.2 weight per cent of the charge separated as an organic layer and was recovered. The aqueous layer was extracted with ethyl ether and about 2.2 weight per cent of the charge recovered. The organic material recovered from the extract of the causticized aqueous solution was combined with the organic material which separated upon causticizing the reaction mixture and the whole dissolved in about per cent as much ethanol (by weight). The ethanol-oil mixture was warmed on a steam-bath (7 0-80 C.) for about 20 minutes and allowed to stand at room temperature (25). The process of crystallization requires several days but can be accelerated by removing the crystals as they are formed. The crude crystals were recrystallized from ethanol and about 5.3 weight per cent of the charge recovered as crystals having a melting point of 126-127 C. The alcohol from which the crystals were first obtained was evaporated and about 4.75 weight per cent of the charge recovered as an oil comprising compounds of other types which are produced in this reaction.

Example III About 0.04 mole of phenyl substituted tetrahydro-1,3-oxazine hydrochloride, about 0.018 mole of formaldehyde (as 36 per cent aqueous solution) and an equal amount of alcohol were mixed and heated to reflux on a steam-bath for about one hour. The mixture was then cooled to room temperature. Thereafter the alcoholic reaction mixture was seeded with a crystal of authentic bis-(phenyl-substituted-tetrahydro 1,3 oxazino) -methane whereupon crystallization began almost immediately. The crystals were separated from the mother liquor. A mixed melting point of a mixture of these crystals with crystals from an authentic sample of bis-(phenyl-substitutedtetrahydro-l,3-oxazino) -methane showed no depression of the melting point. About 25 per cent more crystals were obtained by concentration of the mother liquor.

The foregoing procedure establishes that compound V can be prepared from compound III.

In the manner described in Example II the effect upon the yield of crystalline compound V of the reaction time at a temperature appreciably acorn is above or below 60 C. was investigated. .Thefollowing tabulation presents the results:

61 temperatures about 66 C. and preferably at re-" flux temperature for periods of time in excess of:

EFFECT OF TIME AND TEMPERATURE ON YIELD OF V Molal Proportions oi Reactants B Recovered Crystalline Crystalline R 11: 3? ggi Organic 21223 Portion, Portion Run No. Temperature, C. Denture Layert, Igor- Oi Op Pgrcent of (V), Percon 0 rganie cent of 0-0 01120 NH3(HX) Above 60 Charge 1 Iggni; Layer Charge R! R!!! y 51 l 4 2 Heated to 53 0.; kept 0 15.2 29.0 28.5 4.34 between 50 and 53 C. by external cooling. 50 1 4 2 Heated to 60 0.; kept 27 minutes 13.9 34.1 39. 6 5.51

between 60 and 63 C. by external cooling. 48 1 4 2 Heated to 65 C.; tem- 50 minutes 12.. 3 57.2 37.3 4. 59

perature rose to 74 C. 49 l 4 2 Heated to 60 0.; tem- '70 minutes 11.8 59.1 36.2 4.27 peraturc rose to 74 C. 52 l 2. 24 1.11 Hgzgte to reflux 80 6 hours 14. 3 O 0 53 n 1 2. 24 1.11 '24 hours 2 5. 7 0 0 1 Contains undetermined amounts of 4-substituted-l,3-dioxane. 2 Mostly unreacted RRC=C RR 3 Prolonged heating led to the formation of large amounts of the N-methyl derivative of the substituted tetrahydro-l,3-oxazine. 4 Picrate showed the material to be partially N-methyl-substituted tetrahydro lfi-oxazine.

The foregoing data established that when an olefinic compound, RR'C=CR"R"' as defined herein is reacted with formaldehyde and an ammonium halide in molal proportions in excess of 1:2:2, the yield of crystalline bis-(substitutedtetrahydro-l,3-oxazino)-methane is affected by the residence time at temperatures above 60 C. but below about 70 C. and that a maximum yield of crystalline bis-methane is obtained. when a residence time is of the order of 25 to minutes.

Methylene bridge derivatives of olefinic compounds having a composition represented by the formula RR'C=CR"R"' can be prepared from a variety of olefinic compounds. However, it is to be noted that the bis-methane derivatives are not all readily crystallizable. Thus, for example, the bis-methane derivatives of neopentyl-methyltetrahydro 1,3 oxazine (from diisobutylene, formaldehyde and ammonium chloride) and the bis-methane derivative of dimethyltetrahydro- 1,3-oxazine (from isobutylene, formaldehyde and ammonium chloride) were prepared in the manner described in Example III. However, the bismethane derivatives could not be crystallized.

It is also to be noted that the data presented in the foregoing tabulation establishes that when the olefinic compound RR'C=CR"R"', formaldehyde and ammonium chloride are reacted in molal proportions of less than 114:2 and subjected to prolonged heating, large amounts of the N-methyl derivative of the substituted tetrahyclro-1,3-oxazine,

R OCH2NCH3 R4 CH2 two hours and preferably of the order of four to eight hours.

In the foregoing it has been established that prolonged heating of an olefinic compound, formaldehyde and ammonium halide in a molal proportion such that there are less than four moles of formaldehyde and less than two moles of ammonium halide per mole of olefinic compound yields only an oil and no recoverable crystalline bis-methane. It will now be established that the oil formed is primarily N-methyl-substitutedtetrahydro-1,3-oxazine,

.Percent. Percent Percent Carbon Hydrogen Nitrogen Calculated for oflnuNioa 50.25 4.43 13.79 Observed 50. 21 '3. 55 14. 34

The material prepared as described in the following example was shown to be the same since the mixed melting point for the mixture of the picrate of the N -methyl-phenyl substituted tetrahydro-1,3-oxazine prepared from methylamine hydrochloride and of the picrate of the N- methyl-phenyl substituted tetrahydro-lfi-oxa- The product of the reaction of these mazine prepared as described in' Example IV showed no depression.

Example IV About 10 moles of styrene CGH5CH=CH2, about 21.6 moles of formaldehyde (36 per cent aqueous solution) and about 11.1 moles of ammonium halide were mixed together and warmed to about 65 C. The reaction temperature rose to about 83 C. and was maintained at that level by external cooling. After about 30 minutes, when the heat of reaction had subsided, the material was heated to reflux for about 24 hours. The amine was isolated by extracting the reaction mixture after removal of the organic layer with ethyl ether and causticizing the extracted reaction mixture with sodium hydroxide and separating the free, substantially water-insoluble, amine. The amine was distilled in vacuo.

A small portion of the distilled amine was shaken for fifteen minutes with about 2.6 times by weight as much aqueous 9 per cent hydrochloric acid and the mixture extracted with ethyl ether. Evaporation of the ether yielded a neutral material in 50 per cent yield based on the amount of distilled amine treated. Distillation of the material thus obtained established that it was predominantly phenyl substituted-1,3-dioxane,

Calculated for Observed OHHISNO Percent Carbon 74. 5 73.18 Percent Hydrogen 8. 46 8. 47 Percent Nitrogen 7. 91 7. 83

A picrate was made of the crude distilled amine; i. e., material from which m-dioxane had not been removed; the picrate had a melting point of 7158 C. The picrate was analyzed with the results set forth hereinafter:

Nitrogen, Percent Calculated f0! CnHiaNrOt 13. 79 Observed 13. 23

This picrate was mixed with the picrate of authentic N-methyl-phenyl substituted tetrahydro-1,3-oxazine (prepared as described hereinbefore) and the melting point found to be 157- 158 C.; i. e., no depression of the melting point was observed.

In a similar manner the yields of bis-methane compounds of the various olefinic compounds enumerated in the co-pending application men- 8. tioned hereinbefore can be increased by applying the principles of the present invention to the disclosure of the co-pending application. Thus, the following bis-methanes can be prepared in increased yields as compared to those obtained by following the procedure disclosed in the aforesaid co-pending application: bis-(dimethyl-tetrahydro-1,3-oxazino)-methane from isobutylene; bis (methyl phenyl tetrahydro 1,3 oxazino) methane; bis (ethylhexyl tetrahydro- 1,3 oxazino) methane; bis (methylpentyltetrahydro 1,3 oxazino) methane; bis- (ethyl butyl 1,3 tetrahydro oxazino)- methane; bis (methyl isopropyl tetrahydro- 1,3oxazino)-methane; and others such a described in the co-pending application Serial No. 129,948 to which reference has been made hereinbefore. In general, the hereindescribed method is useful for preparing in improved yield the bis (substituted tetrahydro 1,3 oxazino)- methanes described in the aforesaid co-pending application from olefinic compounds having a composition corresponding to the formula in which R is hydrogen, an alkyl group having less than 17 carbon atoms, an aryl group, an alkaryl group in which the alkyl substituent has less than 9 carbon atoms, an aralkyl group in which the alkyl portion of the group has less than 9 carbon atoms, a cycloalkyl group, and a heterocyclic group; R is R, hydrogen, an alkyl group having less than 17 carbon atoms, an aryl group, an alkaryl group in which the alkyl substituent has less than 9 carbon atoms, an aralkyl group in which the alkyl portion of the group has less than 9 carbon atoms, a cycloalkyl group, and a heterocyclic group, R is R, R, hydrogen, an alkyl group having less than 17 carbon atoms, an aryl group, an alkaryl group in which the alkyl substituent has less than 9 carbon atoms, an aralkyl group in which the alkyl portion of the group has less than 9 carbon atoms, a cycloalkyl group, and a heterocyclic group; and R is R, R, R", hydrogen, an alkyl group having less than 1'7 carbon atoms, an aryl group, an alkaryl group in which the alkyl substituent has less than 9 carbon atoms, an aralkyl group in which the alkyl portion of the group has less than 9 carbon atoms, a cycloalkyl group, and a heterocyclic group. Furthermore, when any of R, R, R and. R is other than H or CH3, it may be substituted with such groups as N02, CN, X, COOH, etc. (X=Cl, Br or I). These substituents preferably are removed by at least 2 carbon atoms from the olefinic moiety. However, there are two limitations, to wit: no more than three and preferably, only two, of R, R, R and R may be substituents other than hydrogen and when one of the pair of substituents, R, R or R",'R' is hydrogen and the other substituents, R" and R or R and R are hydrogen, then the other member of the pair shall be a substituent having a double bond in conjugation with the double bond of the parent olefin. Thus, for example, when R or R is hydrogen and R and R are hydrogen, the other substituent shall be a substituent having a double bond in conjugation with the double bond in the parent olefin. Similarly, when R or R is hydrogen and R and R are hydrogen, the other substituent shall be one having a double bond in comugation with the double bond of the parent olefin. In the aforesaid co-pending application Serial No. 129,948 the following olefinic compounds, coming within the scope of the class defined hereinbefore, are enumerated: styrene, A9,11-linolcic acid, eleostearic acid, A9,11,13-octadecatriencic acid, and similar carboxylic acids having two or more conjugated double bonds, methacrylic acid, isocrotonic acid, vinyl sulfones, vinyl ethers, vinyl thioethers and vinyl halides, diisobutylene, alpha-methyl styrene, isobutylene, l-butene, a miXture of divinylbenzene, diethylbenzene and ethylvinylbenzene, 2-ethyl-l-hexene, 2methyl-l-pentene, 2-ethyl-l-butene, allyl alcohol, betapinene, dipentene, 2-ethyl-2-butene, 2,3- dimethyl l butene, 2,3 dimethyl 1 pentene, 2-methyl-1-heptene, 2,3-dimethyl-1-hexene, 2,3,4 trimethyl 1 pentene, 3 methyl 2- isopropyl 1 butene, 2 methyl 2 undecene, 2 methyl 2 heptadecene, 1 phenyl 1- butene, 2 phenyl 4 methyl 2 hexene, 2- cyclopropyl 1 propene, 1 isopropenyl 2- methyl 3 cyclohexene, 1 methyl 4 isopropenyl l cyclohexene, 1,2 diphenylethylene, vinylphenol, 3-vinylguaiacol, vinylacrylic acid, propenylguaiacol, 2-vinylthiophene, 2- methyl 4 vinylthiophene, 1 furyl 1 butene, vinylpyridine, l-pyrryl-1-propene, halogenated vinyl sulfones such as alpha-chlorovinyl-betachloroethyl sulione, aryl and alkyl vinyl sulfones such as benzylpropenyl sulfone, dimethylallyl ether, vinyl thioether, Vinyl halides, such as CH2=CHCL CH-CHzBr, (CHa)2C=CHBr.

We claim:

1. A process for obtaining improved yields of bis-methanes having the formula,

which comprises reacting an olefinic compound having the formula, RRC:CR"R"', with formaldehyde and an ammonium halide, in a molar proportion of at least 2.5 moles of formaldehyde per mole of said olefinic compound, at a temperature of between about 55 C. and about 70 C., and for between about minutes and about minutes; R,R,R", and R being selected from the group consisting of hydrogen atoms, alkyl radicals having not more than 16 carbon atoms, hydroxyalkyl radicals, carboxyalkyl radicals, OX0- alkyl radicals, a phenyl radical, alkaryl radicals having not more than 8 carbon atoms in the alkyl group thereof, alkenylaryl radicals having not more than 8 carbon atoms in the alkenyl group thereof, thienyl radicals, furyl radicals, and pyridyl radicals.

2. A process for obtaining improved yields of bis (phenyltetrahydro l,3,-oxazino) -methane, which comprises reacting styrene, formaldehyde, and ammonium chloride in a molar proportion of at least 2.5: 1:1, respectively, at a temperature of between about C. and about C., and for a period of time of between about 25 minutes and about 30 minutes.

HOWARD D. HARTOUGH. JOSEPH J. DICKERT, JR. SEYMOUR L. MEISEL.

References Cited in the file of this patent UNITED STATES PATENTS Number Name Date 1,726,713 North Sept. 3, 1929 2,114,121 Bender Apr. 12, 1938 2,243,295 Susie et a1 May 27, 1941 3,319,848 Clark et al May 25, 1943 2,447,822 Senkus Aug. 24, 1948 2,453,086 Caesar Nov. 2, 1948 2,458,526 O-berright Jan. 11, 1949 OTHER REFERENCES Lukasiewiez et al., J. Am. Chem. Soc., vol. 68, DD. 1389-1390 (1946).

Kohn, Monatshefte, vol. 25 (1904) pp. 819 and 841 (complete article p. 817-849) 

1. A PROCESS FOR OBTAINING IMPROVED YIELDS OF BIS-METHANES HAVING THE FORMULA, 